Determination of the sensitivity of a tablet formulation to variations in excipient levels and processing conditions using optimization techniques

Abstract

In anticipation of scale-up activities, a stressing study was conducted on a directly compressible tablet formulation to assess its sensitivity to changes in selected formulation and processing variables. Mathematical modeling and computer-assisted multiple regression analysis, techniques often used in optimization studies, were employed to evaluate the ability of the formulation to withstand these variations without producing detrimental effects upon manufacturing characteristics and tablet performance. The term ‘optimization’ does not precisely describe the activities of this study since the goal was to demonstrate the acceptability and ruggedness of the existing formulation rather than pursue the perfectly optimal formulation. Empirical equations were determined using response-surface modeling techniques and minimum and maximum values of all response variables calculated. These minimum and maximum values were used to demonstrate the ruggedness of the formulation to processing variables. The formulation proved to be quite durable within the ranges of the variables tested, showing only minimal changes in the monitored response variables.